A. Roberto et al., UPTAKE OF 7,12-DIMETHYLBENZ(A)ANTHRACENE AND BENZO(A)PYRENE IN MELANIN-CONTAINING TISSUES, Pharmacology & toxicology, 79(2), 1996, pp. 92-99
It is widely accepted that UV exposure is the main etiological factor
for malignant melanoma. Epidemiologic studies, however, have indicated
that also chemical carcinogens may be a risk factor for the disease.
Polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracen
e and benzo(a)pyrene represent an important class of carcinogenic chem
icals. It is known that 7,12-dimethylbenz(a)anthracene can induce mela
notic tumours in various animal species, and human melanocytes in cult
ure have been found to be capable of metabolizing benzo(a)pyrene to it
s proximate carcinogen benzo(a)pyrene-7,8-diol. In the present study t
he disposition of C-14- and H-3-7, 12-dimethylbenz(a)anthracene and C-
14-benzo(a)pyrene was studied in pigmented and albino mice and Syrian
golden hamsters by whole-body autoradiography. The results showed pron
ounced retention of label in the melanin-containing structures of the
eyes and the hair follicles in the pigmented animals. The labelling of
the corresponding structures in the albino animals was low. Additiona
l experiments showed that 7,12-dimethylbenz(a)anthracene and benzo(a)p
yrene as well as some of their metabolites are bound to melanin in vit
ro. The specific localization of the polycyclic aromatic hydrocarbons
in pigmented tissues due to melanin affinity, combined with bioactivat
ing capacity of melanocytes, suggest that these substances may play a
role in the induction of malignant melanoma.